title: Mesenchymal stem/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential.
abstract: BACKGROUND
  Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity and endometrial cancer.
  
  
  OBJECTIVE
  We hypothesized that an altered endocrine/metabolic environment in PCOS may result in an endometrial "disease phenotype" affecting the gene expression of different endometrial cell populations, including stem cells and their differentiated progeny.
  
  
  METHODS
  This was a prospective study conducted at an academic medical center.
  
  
  METHODS
  Proliferative-phase endometrium was obtained from 6 overweight/obese PCOS (National Institutes of Health criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting-isolated endometrial epithelial cells (eEPs), endothelial cells, stromal fibroblasts (eSFs), and mesenchymal stem cells (eMSCs). Gene expression data were validated using microfluidic quantitative RT-PCR and immunohistochemistry.
  
  
  RESULTS
  The comparison between eEP(PCOS) and eEP(Ctrl) showed dysregulation of inflammatory genes and genes with oncogenic potential (CCL2, IL-6, ORM1, TNAIFP6, SFRP4, SPARC). eSF(PCOS) and eSF(Ctrl) showed up-regulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSC(PCOS) vs eMSC(Ctrl), the most up-regulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). Immunohistochemistry scoring showed increased expression of CCL2 in eEP(PCOS) and eSF(PCOS) compared with eEP(Ctrl) and eSF(Ctrl) and IL-6 in eEP(PCOS) compared with eEP(Ctrl).
  
  
  CONCLUSIONS
  Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and prooncogenic changes, independent of body mass index, especially in eEP(PCOS) and eMSC(PCOS), compared with controls. The study reveals an endometrial disease phenotype in women with PCOS with potential negative effects on endometrial function and long-term health.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143-0132, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Piltonen
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: D W
authors.initials: DW
authors.lastname: Erikson
authors.forename: T L B
authors.initials: TL
authors.lastname: Spitzer
authors.forename: F
authors.initials: F
authors.lastname: Barragan
authors.forename: J T
authors.initials: JT
authors.lastname: Rabban
authors.forename: H
authors.initials: H
authors.lastname: Huddleston
authors.forename: J C
authors.initials: JC
authors.lastname: Irwin
authors.forename: L C
authors.initials: LC
authors.lastname: Giudice
mesh_terms: D000328:Adult; D015992:Body Mass Index; D049109:Cell Proliferation; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050177:Overweight / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8